The simian immunodeficiency virus (SIV) macaque model has been used in attempts to develop an effective vaccine to prevent AIDS in monkeys. Inactivated whole virus vaccines have been shown to protect macaques against SIV infection. It has recently been shown that part of this protection was due to cellular antigens in the vaccine preparations and in the virus challenge stocks. We have identified the major cellular proteins present in SIV and HIV virus preparations and shown that antibodies to these proteins (beta-2 microglobulin and HLA DR) neutralize SIV and HIV virus infectivity in vitro. Experiments are underway to test if antibodies to these purified proteins will protect macaques in vivo from SIV infection. These results may have important implications in the design of effective HIV vaccines. We have also shown that protective immunity in macaques can be elicited by immunization with a recombinant vaccinia virus expressing SIV/Mne gp160 followed by boosting with gp160. The immunized animals were protected against a low-dose intravenous challenge of the homologous virus. Since only recombinant immunogens were used and no anti-cellular antibodies were detected in the immunized animals, these results demonstrated that immune responses against viral envelope glycoproteins were sufficient to protect against homologous virus infections. This combination immunization regimen is similar to one currently being evaluated in human volunteers using analogously constructed HIV-1 vaccines. Pig-tailed macaques are unique among macaques in being susceptible to HIV- 1 infection in vitro and in vivo. In order to quantitate the amount of HIV-1 needed to infect pig-tailed macaques, the HIV-1 III B in stock that has been titered in chimpanzees (and used in all subsequent challenges) is being titered in these macaques. The results will determine the immediate applicability of the HIV-1/ pig-tailed macaque model for studies of HIV antiviral and vaccine regimens.